Giant cell arteritis (GCA), the most common form of systemic necrotizing vasculitis, is a chronic inflammatory condition of unknown etiology that chiefly afflicts the elderly. Many features of the disorder suggest a chronic bacterial infection, but few investigations of this hypothesis have been conducted. During this decade, unexpected links between infections and a diverse group of diseases have been established. The list of these diseases includes atherosclerosis, another chronic inflammatory condition with a predilection for affecting medium- and large-sized arteries in the elderly. We have conducted two small preliminary studies indicating that Chlamydia pneumoniae, an obligate intracellular pathogen recently implicated in the pathogenesis of atherosclerosis, is a candidate for a role in the pathogenesis of GCA. In this proposal, we describe plans to correlate the presence of bacterial infections in temporal artery specimens and the diagnosis of GCA. We will exploit the large number of temporal artery biopsies stored at our institution (n = 500), our expertise in the use of polymerase chain reaction (PCR) techniques, and our knowledge and experience with the clinical presentation of GCA. We plan to study the temporal artery biopsies of 92 subjects with GCA (positive temporal artery biopsies) and 92 control subjects whose temporal artery biopsies were negative and whose clinical courses were inconsistent with GCA. In addition to investigating the role of C. pneumoniae, we will also employ broad-range 16S rRNA PCR primers to correlate GCA with the possible presence of DNA from all other species of Eubacteriales. This approach will permit us to examine the correlation between GCA and any species of bacteria known (or as yet unknown) to be relevant to human disease. We will also measure the serological response to C. pneumoniae by microimmunofluoresence in a group of prospectively-collected GCA cases and 2 control groups. This study represents a new approach to investigating the pathogenesis of GCA. Our results may lead to new approaches to the therapy of GCA, a chronic condition currently associated with a toxic treatment (prolonged corticosteroid use). Our approach may also be extrapolated to the study of other vasculitides.